Drug Design Laboratory
Current Projects
The Drug Design Laboratory uses computer-aided molecular modelling techniques to drive the development of novel bioactive compounds. Following their design, candidate molecules are synthesised by members of the laboratory and evaluated in appropriate in vitro and in vivo assays. Data from these assays are then used to hone the design process, with the goal of producing more active molecules.
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Growth factors
Growth factors are naturally-occurring proteins which regulate the growth and survival of cells. Their potent biological effects make them attractive targets for the development of novel therapeutic agents for a multitude of as yet untreatable diseases. However, because of their poor pharmacokinetic properties — the physical size and chemical nature of proteins renders them highly susceptible to breakdown in the bloodstream, requires that they be injected, and limits their access to certain areas of the body — recombinant proteins themselves are unlikely to be the optimal agents for clinical use. We have developed techniques that enable us to design conformationally-constrained peptides that act as potent mimetics or inhibitors of selected growth factors. Currently targets include brain-derived neurotrophic factor, mimetics of the hormone relaxin (in collaboration with A/Prof John Wade), and vascular endothelial growth factors (in collaboration with Drs Marc Achen and Steve Stacker). The latter collaboration received an important fillip late in 2003, in the form of an NHMRC Program Grant awarded to our collaborators.
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Calibre Biotechnology Pty Ltd
Calibre Biotechnology – a startup company established by Dr Hughes – achieved its first milestones in 2003, and thus secured continuing funding from its major investor UniSeed, and the Commonwealth Government (via a Biotechnology Innovation Fund). Calibre is continuing to develop BDNF mimetics for clinical use in the treatment of neurodegenerative diseases, and to apply its molecular design approach to obtain mimetics and inhibitors of other growth factors of potential therapeutic significance.
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Other Projects
The Drug Design laboratory also collaborates with Associate Professor Alastair Stewart in developing three dimensional structure-activity relationships (3D-QSAR) of 2-methoxyestradiol and synthetic analogues using comparative molecule field analysis (CoMFA) methods, A/Prof Owen Woodman and Dr Spencer Williams examining structure-activity relationships of flavanols, Dr Phil Thompson on the molecular modelling of novel, selective phosphodiesterase inhibitors and Associate Professor Phil Marley and Amanda Donald in the design and synthesis of novel cell-permeable peptides that act as inhibitors of specific G protein signalling pathways.
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